IL-27 controls a diverse range of immune responses in many disease settings. Here, we identify intestinal epithelial cells (IECs) as one of the major IL-27 cellular sources in the gut-associated tissue. Unlike IL-27 secreted by innate immune cells, gut epithelial IL-27 is dispensable for T-bet+ regulatory T cell (T reg cell) differentiation or IL-10 induction. Rather, IEC-derived IL-27 specifically promotes a distinct CD8αα+CD4+ intraepithelial lymphocyte (IEL) population that acquires their functional differentiation at the intestinal epithelium. Loss of IL-27 in IECs leads to a selective defect in CD8αα+CD4+ IELs over time. Consequently, mice with IEC-specific IL-27 ablation exhibited elevated pathogen burden during parasitic infection, and this could be rescued by transfer of exogenous CD8αα+CD4+ IELs. Collectively, our data reveal that in addition to its known regulatory properties in preventing immune hyperactivity, gut epithelial IL-27 confers barrier immunity by inducing a specific IEL subset and further suggest that IL-27 produced by different cell types plays distinct roles in maintaining intestinal homeostasis.

中文翻译：

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肠上皮 IL-27 通过诱导上皮内淋巴细胞赋予肠道免疫力

IL-27 在许多疾病环境中控制多种免疫反应。在这里，我们将肠上皮细胞 (IEC) 确定为肠道相关组织中主要的 IL-27 细胞来源之一。与先天免疫细胞分泌的 IL-27 不同，肠上皮 IL-27 对于 T-bet+ 调节性 T 细胞（T reg 细胞）分化或 IL-10 诱导是可有可无的。相反，IEC 衍生的 IL-27 特异性促进独特的 CD8αα+CD4+ 上皮内淋巴细胞 (IEL) 群体，使其在肠上皮细胞中获得功能分化。随着时间的推移，IEC 中 IL-27 的缺失会导致 CD8αα+CD4+ IEL 选择性缺陷。因此，IEC特异性IL-27消融的小鼠在寄生虫感染期间表现出病原体负荷升高，这可以通过转移外源CD8αα+CD4+ IEL来挽救。总的来说，我们的数据表明，除了其已知的预防免疫过度活跃的调节特性外，肠上皮 IL-27 通过诱导特定的 IEL 子集来赋予屏障免疫，并进一步表明不同细胞类型产生的 IL-27 在维持肠道功能方面发挥着不同的作用。体内平衡。